The research program outlined in the following sections has as an overall objective the elucidation of some of the molecular changes related to the development of alcohol tolerance and the typical alcohol withdrawal reaction. A hypothesis is presented to explain both tolerance to and dependence on ethanol as processes in a continuum resulting from the interference of alcohol with the normal functioning of post synaptic membrane receptors. Alcohol is believed to disrupt membrane proteins, including some receptors, and thereby cause a decrease in neuronal responsiveness. Cellular adaptation, or tolerance, involves the elaboration of more receptor molecules. When the alcohol effect is removed, cellular supersensitivity results from this excess number of receptors and can produce the seizure-like responses of the abstinence syndrome. Experiments are designed to compare the effects of chronic alcohol intoxication on the membrane binding characteristics of acetylcholine, L-glutamate, and GABA. Fluorescent probes will be used to examine the mechanism by which ethanol disrupts membrane receptors and to screen chemical agents which may be effective in preventing withdrawal seizures in vivo.